Over the past several decades, numerous dementia risk factors have been identified, although it is not clear whether all of them are causally associated with dementia risk. Age is well established as the most important risk factor for dementia [4
], but a large number of other risk factors have been identified, including other demographic factors (gender [19
], education [20
] and race/ethnicity [21
]), cardiovascular risk factors (diabetes [22
], hypertension [23
] and stroke [24
]), genetic factors (APOE
], lifestyle factors (physical [26
] and mental activity [27
], diet [28
], smoking [29
] and alcohol consumption [30
]), psychosocial factors (depressive symptoms [31
] and social activity [32
]), cognitive function (low-normal performance on standard tests) [33
], physical function (ability to perform daily activities) [34
], physical performance (performance score [35
] and abnormal gait [36
]), biomarkers (inflammatory markers [37
] and cystatin C [38
]) and MRI findings (hippocampal atrophy, white matter disease and ventricular atrophy) [39
], among others. The goal of a risk index is to determine which combination of factors is most predictive of future risk.
Two dementia risk indices have recently been developed. The first was a Mid-Life Dementia Risk Score developed in Finland that is designed to be administered to middle-aged adults (40–64 years) [41
]. This tool uses a combination of age, gender, education, physical inactivity and history of obesity, hypertension and hypercholesterolemia to predict risk of dementia 20 years later (). The accuracy of the Mid-Life Dementia Risk Score based on the statistical measure of accuracy in which 1.0 is perfect and 0.5 is no better than guessing (c statistic) was 0.77. Inclusion of the genetic risk factor APOE
only slightly improved the accuracy of the index (c statistic: 0.78). In addition, 1% of individuals with the lowest mid-life risk scores developed dementia over 20 years compared with 16% of those with the highest mid-life risk scores. Since this index requires information regarding disease status in mid-life, it may be especially helpful for identifying middle-aged individuals who could be targeted for aggressive treatment of cardiovascular risk factors and behavioral interventions.
Current prognostic indices for dementia.
The second dementia risk index, developed by our group, is a Late-Life Dementia Risk Index that is designed to be administered in older adults (age 65 years or older) [42
]. It uses a combination of demographic, cognitive, behavioral, functional, medical, genetic, cerebral MRI, and carotid artery ultrasound measures to predict risk of developing dementia within 6 years (). The c statistic was 0.81, which was slightly higher than that observed for the Mid-Life Dementia Risk Score. In addition, the Late-Life Dementia Risk Index achieved greater separation between the low- and high-risk groups in terms of actual dementia risk; 4% of subjects with low scores developed dementia within 6 years compared with 23% of subjects with moderate scores and 56% of subjects with high scores.
The Late-Life Dementia Risk Index was initially developed to be a ‘gold-standard’ for predicting dementia risk in late life. However, it includes several measures that may be somewhat costly and time consuming to obtain, such as cerebral MRIs, carotid artery ultrasound and APOE genotype. The Late-Life Index may prove to be useful when extensive clinical testing is being planned or has already been performed or in research settings when it is important to obtain the most accurate prediction of risk possible. However, it may be impractical to administer in many clinical and research settings. Therefore, we are also in the process of developing an abbreviated Brief Dementia Risk Index that will focus on identifying measures that predict dementia risk with high accuracy and could be easily administered by a nurse or research assistant.
It is interesting to note the similarities and differences between the mid- and late-life indices. Older age, lower education/cognitive performance and APOE e4 genotype were identified as important risk factors in both indices. The other factors included in the Mid-Life Score were primarily cardiovascular risk factors (obesity, hypertension, hypercholesterolemia and inactivity). By contrast, the Late-Life Index included several measures that could be viewed as measures of the impact of mid-life risk factors on the brain and other organs (e.g., mid-life hypertension might lead to late-life white matter disease on an MRI; mid-life hypercholesterolemia might lead to late-life internal carotid artery thickening). Consistent with other studies, high BMI was identified as a risk factor in the Mid-Life Score while low BMI was identified as a risk factor in the Late-Life Index.